So-called acyl transfer reactions involve the transfer of an acyl group (the residue of an organic acid after removal of the carboxyl hydroxy group) either internally within a chemical species or from one chemical species to another. Examples are amide formation, trans-esterification and hydrolysis.
It is well known that acyl transfer reactions can be catalyzed by imidazole in aqueous solution, the imidazole, which is a strong nucleophile, forming an intermediary reactive complex with the acyl group. Also polymer-supported imidazoles have been used as acyl transfer catalysts (see e.g. Skjujins, A., et al., Latv. PSR Zinat. Akad. Vestis, Kim. Ser. 1988 (6), 720-5).
It has further been shown that small peptides containing a histidine (His) residue (an amino acid which contains an imidazolyl group) can have hydrolytic activity.
Recent progress in designing structural proteins and peptides has resulted in the preparation of several peptides with substantial catalytic activity (W. F. DeGrado, Nature, 365, 488 (1993). For example, K. Johnsson et al., Nature, 365, 530 (1993) disclose a short self-associating Leu-Lys-rich helical peptide that accelerates the rate of decarboxylation by means of a Schiff's base intermediate between a substrate of oxaloacetate and an amine with an electrostatically depressed acid constant (Ka). It is mentioned that the secondary structure is important for the activity.
Nature's enzymes form powerful catalysts by combining residues that are by themselves only modestly reactive. It is therefore not surprising to find that sites other than those responsible for catalysis also show chemical reactivity and that unexpected reactions can occur on the protein surface. The combination of His with Lys, for example, in a helix forms a simple two-residue site where the Lys activates the His residue in its reactions with active esters and the His activates the Lys1,2. The overall amidation rate of the lysine is at least three orders of magnitude larger than that in the direct reaction between the lysine and the esters1.